AB0518 EFFECT OF LITIFILIMAB ON TYPE I INTERFERON (IFN) BIOMARKERS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) OR CUTANEOUS LUPUS ERYTHEMATOSUS (CLE): RESULT OF THE LILAC PHASE 2 STUDY
Authors: R. Furie, V. Werth, E. Milliman, K. Ferber, F. Casey, R. Brown, D. Raitcheva, J. Zoghbi, D. Graham, G. Kong, Y. Lahoud, N. Franchimont, C. Barbey
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Litifilimab (BIIB059) is a humanised IgG1 monoclonal antibody targeting BDCA2, a receptor predominantly expressed on plasmacytoid dendritic cells, that negatively regulates production of Type I IFN and proinflammatory chemokines and cytokines <sup>[1,2]</sup>. Both Part A (SLE) and Part B (CLE) of the randomised, placebo-controlled Phase 2 LILAC study of litifilimab (NCT02847598) met their primary efficacy endpoints at Weeks 24 and 16, respectively <sup>[1,2]</sup>. <h3>Objectives</h3> To evaluate the effect of litifilimab treatment on IFN gene signature (IFNGS) scores and IFNα levels in LILAC participants. <h3>Methods</h3> Expression of a 22-IFNGS and IFNα concentrations were examined over time in whole blood and serum samples, respectively, from the LILAC modified intent-to-treat population (mITT; Part A N=120, Part B N=132) with a baseline biomarker value and at least one post-baseline value. Treatment effects were estimated using a mixed-effects model repeated measures approach (MMRM) and the dose-response relationship was estimated in Part B using a previously described MCP-Mod method <sup>[2]</sup>. <h3>Results</h3> Few participants had low baseline IFNGS scores, so only data for participants with high baseline IFNGS scores are described here. At the earliest post-baseline timepoint in Part A (Week 1) a sharp reduction in the mean IFNGS score was observed in the litifilimab 450-mg group vs placebo, which was sustained through Week 24 <b>(Figure 1; Table 1</b>). At the earliest timepoint in Part B (Week 2), reductions in mean IFNGS scores were greater than placebo in all three litifilimab dose groups, and the dose effects were sustained through Week 16 <b>(Figure 1; Table 1</b>). A similar pattern of reductions and dose effects was observed with the corresponding IFNα concentrations <b>(Table 1</b>). Statistically significant (P&lt;0.05) changes from baseline in IFNGS scores and IFNα levels were demonstrated for litifilimab 450 mg in Part A and for the 150-mg and 450-mg groups in Part B <b>(Table 1</b>). In Part B, the IFNGS-high subgroup's IFNGS scores and IFNα concentrations showed a similar dose-response relationship as was observed for the mITT's CLE clinical responses <sup>[2]</sup>. <h3>Conclusion</h3> Litifilimab treatment induced sustained reductions in 22-IFNGS and IFNα concentrations in participants with SLE and CLE. <h3>References</h3> [1]Furie RA, et al. N Engl J Med 2022;387:894–904 [2]Werth VP, et al. N Engl J Med 2022;387:321–331 <h3>Acknowledgements</h3> The authors thank the LILAC investigators and their participants for their valuable contributions to this study. Nathalie Franchimont was an employee of Biogen at the time this work was conducted and is currently employed by Nimbus Therapeutics. This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Selene Medical Communications (Macclesfield, UK), funded by Biogen. <h3>Disclosure of Interests</h3> Richard Furie Consultant of: Biogen, Grant/research support from: Biogen, Victoria Werth Consultant of: Abbvie, Amgen, Anaptysbio, AstraZeneca, Biogen, Bristol Myers Squibb, Celgene, CSL Behring, EMD Serono, Galderma, Gilead, GSK, Idera, Janssen, Kyowa Kirin, Lilly, Merck, Nektar, Neovacs, Novartis, Octapharma, Pfizer, Resolve, Rome Pharmaceuticals, Rome Therapeutics, Sanofi, Viela, Xencor, Grant/research support from: Amgen, Argenx, Biogen, Celgene, Corbus, CSL Behring, Genentech/Roche PI, Gilead, Horizon Therapeutics, Janssen, Pfizer, Regeneron, Syntimmune, Ventus, Viela, Eric Milliman Shareholder of: Biogen, Employee of: Biogen, Kyle Ferber Shareholder of: Biogen, Employee of: Biogen, Fergal Casey Shareholder of: Biogen, Employee of: Biogen, Roland Brown Shareholder of: Biogen, Employee of: Biogen, Denitza Raitcheva Shareholder of: Biogen, Employee of: Biogen, Jad Zoghbi Shareholder of: Biogen, Employee of: Biogen, Danielle Graham Shareholder of: Biogen, Employee of: Biogen, George Kong Shareholder of: Biogen, Employee of: Biogen, Youmna Lahoud Shareholder of: Biogen, Employee of: Biogen, Nathalie Franchimont Shareholder of: Biogen, Nimbus Therapeutics, OMass Therapeutics, Employee of: Biogen (past employee), Nimbus Therapeutics (current employee), OMass Therapeutics (board of directors), Catherine Barbey Shareholder of: Biogen, Employee of: Biogen.